Synlogic Presents Data from Phase 1/2a Study of SYNB1618 at the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM)

Synlogic, Inc., (Nasdaq: SYBX), a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, today announced presentation of the full clinical data set from healthy volunteers and patient cohorts of a randomized, double-blind, placebo-controlled Phase 1/2a study of SYNB1618, which is being developed as an oral therapy for the treatment of phenylketonuria (PKU). The data were presented by Jerry Vockley, M.D. Ph.D., Professor of Pediatrics and Chief of Medical Genetics, University of Pittsburgh, on September 4, 2019 at the annual symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) in Rotterdam.

“Lifetime dietary management of PKU is effective but challenging for patients and there remains a significant unmet need for this population,” said Dr. Vockley, who was a principal investigator on Synlogic’s study. “Physicians, patients and families welcome the development of novel therapies like SYNB1618 that have the potential to impact the lives of all PKU patients.”

The study’s primary objectives were to evaluate safety and tolerability of an early liquid formulation of SYNB1618, as well as clearance of SYNB1618 from the gastrointestinal (GI) tract after cessation of dosing. Exploratory outcomes were related to the assessment of the pharmacodynamic effects of SYNB1618, including measurement of previously identified biomarkers related to SYNB1618’s engineered ability to consume phenylalanine (Phe).

“With this study, we have taken another step towards our goal of delivering a safe, oral therapy option for all patients with PKU regardless of age or disease type,” said Aoife Brennan, M.B., B.Ch., Synlogic’s president and chief executive officer. “These important data have informed advancement of SYNB1618 and, more broadly, have demonstrated the potential of our Synthetic Biotic development platform to deliver novel medicines designed to perform a therapeutic function.”

Synlogic’s Synthetic Biotic platform leverages the tools and principles of synthetic biology to engineer a non-pathogenic strain of E. coli (Nissle) to perform or deliver specific functions lost or damaged due to disease. SYNB1618, designed to function in the GI tract, has been engineered with two different mechanisms to consume Phe, an essential amino acid that can accumulate to harmful levels in patients with PKU with severe consequences. SYNB1618 is designed to metabolize Phe to harmless compounds including trans-cinnamic acid (TCA) in the blood which is further metabolized in the liver and excreted as hippurate (HA) in the urine. TCA and HA represent specific quantitative biomarkers of SYNB1618 activity as demonstrated by Synlogic’s preclinical data that were published in Nature Biotechnology and in data from healthy volunteers from the first part of this Phase 1/2a study. SYNB1618 is also designed to metabolize Phe to phenylpyruvate (PP) via a second enzyme mechanism, L-amino acid transaminase (LAAD). One of the downstream metabolites of LAAD activity is phenyl-lactic acid (PLA) which can be measured in the urine.